This laboratory is engaged in the study of the functional properties of several blood proteins through an investigation of their structural properties. The major proteins currently under active study are the human serum protein haptoglobin and a human myeloma protein IgG2 Gar. Haptoglobin is a serum protein that complexes very strongly with red cell-free hemoglobin. Our interest is to determine as much as we can about the nature of the haptoglobin molecule and its specific interaction with hemoglobin. This study is being pursued by a variety of approaches, including crystallography, biochemistry and model-building. Crystals of the full complex have been obtained and are being pursued vigorously. Residues involved in the contact interactions are being identified by studying changes in the binding constant of chemically modified hemoglobins and haptoglobins, mutant hemoglobins and proteolyzed haptoglobins. A model of the haptoglobin heavy chain has been built by comparative model building. The assembly properties of isolated, renatured haptoglobin chains and their interaction with hemoglobin are also being investigated. The human myeloma protein, IgG2Gar binds riboflavin very strongly in vivo and in vitro at a molar ratio of 2:1 and thus is probably a true antigen-antibody complex. Thin crystals of the Fab fragment have been obtained which are being examined by electron microscopy. The nature of the interaction between riboflavin and IgG Gar has been investigated by measuring the binding constant of riboflavin analogues to the IgG.